The invention relates to fragrance and/or antibacterial precursor compounds. In particular, the invention relates to the use of compounds which can act as fragrance and/or antibacterial precursors in cosmetic products such as deodorants and antiperspirants and in laundry products such as detergents and fabric softeners or in air fresheners or hard surface cleaners. These compounds are normally odourless or nearly so, but upon contacting the skin as for example, in skin care compositions or in personal care compositions, produce fragrances. The compounds also produce fragrances when used in the presence of enzymes such as lipases and proteases, e.g. used in (laundry) detergents and fabric softeners, thus providing a prolongation of the fabric scenting effect. The compounds can also produce fragrances when heated.
A principal strategy currently employed in imparting odours to consumer products is the admixing of the fragrance directly into the product. There are however, several drawbacks to this strategy. The fragrance material can be too volatile, resulting in fragrance loss during manufacturing, storage, and use. Many fragrance materials are also unstable over time. This again results in loss during storage.
In some cases, fragrances are microencapsulated or treated with cyclodextrins to form inclusion complexes to help decrease volatility and improve stability. However, these methods are for a number of reasons often not successful. In addition, cyclodextrins can be too expensive.
In many consumer products it is desirable for the fragrance to be released slowly over time. Microencapsulation and cyclodextrins have been used to provide slow-release properties, however, they are subject to the same limitations as above.
The present invention now provides compounds which show a low level of odour, or are even odourless, and can be cleaved under activating conditions, e.g. by heat or by an acid, a base, bacteria or enzymes, to give fragrant molecules. So, for example, the compounds of the invention are odourless prior to application to the skin, but release fragrant molecules after application to the skin, that is, they provide a delayed release of the fragrance, in particular to the skin in the axilla which is the result of the cleavage by bacteria. The compounds of the present invention also release fragrant molecules when used in the presence of enzyme-containing products and, this way, provide a prolongation of the fabric scenting effect. The compounds of the present invention also release fragrant molecules when heated.
The compounds under consideration are compounds of the formula 
in which n is 1, 2 or 3 and R1 to R6 represent, independently, branched or unbranched, substituted or unsubstituted alkyl-, alkenyl-, alkinyl-, cycloalkyl-, cycloalkenyl- or aromatic-radicals or hydrogen wherein these radicals may in addition contain one or more xe2x80x94Oxe2x80x94 and/or 
groups, whereby one or two rings can be build by the combination of the respective R1 to R6 and this/these ring(s) can be further substituted by an alkyl-group, in which X is either O and R7 represents a radical of an alcohol or phenol R7OH or X is N and R7 represents the radical of an amine R7xe2x80x2R7xe2x80x3NH, whereby R7xe2x80x2 and R7xe2x80x3 represent independently, branched or unbranched, substituted or unsubstituted alkyl-, alkenyl-, alkinyl-, cycloalkyl-, cycloalkenyl- or aromatic radicals or either R7xe2x80x2 R7xe2x80x3 may be hydrogen, whereby the amine is a fragrant amine or the amine has more than 9 C atoms, whereby R7 of the alcohol or phenol and R7xe2x80x2 and/or R7xe2x80x3 of the amine, respectively, may further contain at least one remaining part C(OH)R1R2xe2x80x94CR3R4xe2x80x94(CR5R6)nxe2x80x94COxe2x80x94 of formula I. Thus, the precursor compounds are esters of formula Ia 
in which n is 1, 2 or 3 and R1 to R6 represent, independently, branched or unbranched, substituted or unsubstituted alkyl-, alkenyl-, alkinyl-, cycloalkyl-, cycloalkenyl- or aromatic-radicals or hydrogen wherein these radicals may in addition contain one or more xe2x80x94Oxe2x80x94 and /or 
groups, R7 represents a radical of an alcohol or phenol R7OH, whereby one or two rings can be build by the combination of the respective R1 to R6 and this/these ring(s) can be further substituted by an alkyl-group, whereby R7 may further contain the remaining part C(OH)R1R2xe2x80x94CR3R4xe2x80x94(CR5R6)nxe2x80x94COxe2x80x94 of formula Ia, or amides of formula Ib 
in which n is 1, 2 or 3 and R1 to R6 represent, independently, branched or unbranched, substituted or unsubstituted alkyl-, alkenyl-, alkinyl-, cycloalkyl-, cycloalkenyl- or aromatic-radicals or hydrogen wherein these radicals may in addition contain one or more xe2x80x94Oxe2x80x94 and /or 
groups, whereby one or two rings can be build by the combination of the respective R1 to R6 and this/these ring(s) can be further substituted by an alkyl-group, and R7 represents a radical of an amine R7xe2x80x2R7xe2x80x3NH, whereby R7xe2x80x2 and R7xe2x80x3 represent, independently, branched or unbranched, substituted or unsubstituted alkyl-, alkenyl-, alkinyl-, cycloalkyl-, cycloalkenyl- or aromatic radicals or either R7xe2x80x2 or R7xe2x80x3 may be hydrogen, whereby the amine is a fragrant amine or the amine has more than 9 C atoms, whereby R7xe2x80x2 and/or R7xe2x80x3 may further contain at least one remaining part C(OH)R1R2xe2x80x94CR3R4xe2x80x94(CR5R6)nxe2x80x94COxe2x80x94 of formula Ib. With respect to the precursor compounds of formula Ia specifically the invention is related to those compounds in which n is 1, 2 or 3 and R1 to R6 represent, independently, substituted or unsubstituted alkyl-, alkenyl-, alkinyl-, cycloalkyl-, cycloalkenyl- or aromatic-radicals or hydrogen wherein these radicals may in addition contain one or more xe2x80x94Oxe2x80x94 and/or 
groups, R7 represents a radical of a fragrant alcohol R7OH, whereby one or two rings can be build by the combination of the respective R1 to R6 and this/these ring(s) can be further substituted by an alkyl-group.
Further characteristics and advantages of the invention are described by claims 4 to 29 and by the following description and examples.
The compounds of formula I are not limited to any particular stereoisomers, all possible stereoisomers (enantiomers, diastereomers) and all mixtures are thus included within the scope of formula I.
The compounds of formula I may preferably be used as sustained release odorants but also to mask or attenuate undesirable odours or to provide additional odours not initially present in consumer products, i.e. laundry detergents, fabric softeners, fabric softeners sheets, hard surface cleaners, automatic dishwasher detergents and (other) enzyme-containing consumer products. Additional applications include cosmetic products destined for application to human skin such as underarm deodorants or antiperspirants or other deodorants contacting the body, or in hand lotions, baby powders, baby lotions, ointments, foot products, facial cleansers, body wipes, facial make-up, colognes, after-shave lotions, shaving creams, etc. Further additional applications include ironing treatments and air fresheners dispensed via heat.
The compounds of formula I may be used individually in an amount effective to enhance the characteristic odour of a material. More commonly, however, the compounds are mixed with other fragrance components in an amount sufficient to provide the desired odour characteristics.
The amount required to produce the desired, overall effect varies depending upon the particular compounds of formula I chosen, the product in which it will be used, and the particular effect desired.
For example, depending upon the selection and concentration of the compound(s) of formula I chosen, when added either singly or as a mixture, e.g. to a deodorant, laundry product, hard surface cleaner or air freshener composition at levels ranging from about 0.1 to about 10% by weight, or most preferred about 0.25 to about 4% by weight, an odorant, i.e. an odoriferous alcohol and an odoriferous lactone in an organoleptically effective amount is released when the product is used. These newly formed odorants serve to enhance the odour of the fragrance.
The compounds of formula I can accordingly be used in the manufacture of odorant compositions used in the preparation of air fresheners, cosmetic and laundry products e.g. deodorants, antiperspirants, laundry detergents, fabric softeners, hard surface cleaners, and as is evident from the above compilation, a broad range of known odorants or odorant mixtures can be used. In the manufacture of such compositions the known odorants or odorant mixtures set forth above can be used according to methods known to a person skilled in the art, normally a perfumer, or described e.g. in W. A. Poucher, Perfumes, Cosmetics, Soaps, 2, 7th Edition, Chapman and Hall, London 1974.
Concerning the esters suitable examples of odoriferous alcohols R7OH are alcohols or phenols such as listed in Table 1.
amyl alcohol
hexyl alcohol*
hexyl alcohol*
heptyl alcohol*
octyl alcohol*
nonyl alcohol*
decyl alcohol*
undecyl alcohol*
lauryl alcohol*
myristic alcohol
3-methyl-but-2-en-1-ol*
3-methyl-1-pentanol
cis-3-hexenol**
cis-4-hexenol*
3,5,5-trimethyl hexanol
3,4,5,6,6-pentamethylheptan-2-ol*
citronellol**
geraniol**
oct-1-en-3-ol
2,5,7-trimethyl octan-3-ol
2-cis-3,7-dimethyl-2,6-octadien-1-ol
6-ethyl-3-methyl-5-octen-1-ol*
3,7-dimethyl-oct-3,6-dienol*
3,7-dimethyloctanol**
7-methoxy-3,7-dimethyl-octan-2-ol*
cis-6-nonenol*
5-ethyl-2-nonanol
6,8-dimethyl-2-nonanol*
2,2,8-trimethyl-7 (8)-nonene-3-ol
nona-2,6-dien-1-ol
4-methyl-3-decen-5-ol**
dec-9-en-1-ol
benzylalcohol
2-methyl undecanol
10-undecen-1-ol
1-phenyl ethanol*
2-phenyl ethanol**
2-methyl-3-phenyl-3-propenol
2-phenyl propanol*
3-phenyl propanol*
4-phenyl-2-butanol
2-methyl-5-phenyl pentanol*
2-methyl-4-phenyl-pentanol*
3-methyl-5-phenyl-pentanol*
2-(2-methylphenyl)-ethanol*
4-(1-methylethyl)benzene methanol
4-(4-hydroxyphenyl)butan-2-one*
2-phenoxy ethanol*
4-(1-methylethyl)-2-hydroxy-1-methyl benzene
2-methoxy-4-methyl phenol
4-methyl phenol
anisic alcohol*
p-tolyl alcohol*
cinnamic alcohol**
vanillin*
ethyl vanillin*
eugenol**
isoeugenol**
thymol
anethol*
decahydro 2-naphthalenol
borneol*
cedrenol*
farnesol*
fenchyl alcohol*
menthol* 3,7,11-trimethyl-2,6,10-dodecatrien-1-ol alpha ionol* tetrahydro ionol*
2-(1,1-dimethylethyl)cyclohexanol*
3-(1,1-dimethylethyl)cyclohexanol*
4-(1,1-dimethylethyl)cyclohexanol*
4-isopropyl cyclohexanol
6,6-dimethyl-bicyclo [3.3.1]hept-2-ene-2-ethanol
6,6-dimethyl-bicyclo [3.1.1]hept-2-ene-methanol*
p-menth-8-en-3-ol*
3,3,5-trimethyl cyclohexanol
2,4,6-trimethyl-3-cyclohexenyl-methanol*
4-(1-methylethyl)cyclohexyl-methanol*
4-(1,1-dimethylethyl)cyclohexanol
2-(1,1-dimethylethyl)-cyclohexanol
2,2,6-trimethyl-alpha-propyl cyclohexane propanol*
5-(2,2,3-trimethyl-3-cyclopentenyl)-3-methylpentan-2-ol*
3-methyl-5-(2,2,3-trimethylcyclopentyl-3-enyl)pent-4-en-2-ol**
2-ethyl-4(2,2,3-trimethylcyclopentyl-3-enyl)but-2-en-1-ol**
4-(5,5,6-trimethylbicyclo[2.2.1]hept-2-yl)-cyclohexanol*
2-(2-methylpropyl)-4-hydroxy-4-methyl-tetrahydropyran*
2-cyclohexyl propanol*
2-(1,1-dimethylethyl)-4-methyl cyclohexanol*
1-(2-tert-butyl-cyclohexyloxy)-2-butanol*
1-(4-isopropyl-cyclohexyl)-ethanol*
linalool **
2,6-dimethyl-heptan-2-ol**
2,6-dimethyl-oct-7-en-2-ol**
whereby one asterisk indicates the preferred alcohols and phenols and two asterisks indicate the more preferred alcohols and phenols.
It is a matter of course, that it is not possible to give a complete list of the odoriferous alcohols and phenols R7OH which are liberated as a result of the desired cleavage of the compounds of formula I as mentioned above, especially by heat, enzymes or by bacteria, and which alcohols are then capable of imparting agreeable odours. The skilled artisan is, however, quite aware of those alcohols and phenols, which provide a positive contribution to the fragrance compositions.
But the alcohol or phenol constituting the radical R7 can also be a non-odoriferous one or a polyalcohol. Thus, the radical R7 can be derived from as well a simple alcohol like e.g. methanol or ethanol as also from a fatty alcohol or a compound such as 7-hydroxy-4-methyl coumarin.
Examples of polyalcohols constituting the radical R7 in the compounds of formula I, or more specifically of formula Ia, are:
diols such as: diethylene glycol, propylene glycol, triethylene glycol, N-butyldiethanol amine, 1,3-bis-(4-hydroxy butyl)-1,1,3,3 tetramethyl-disiloxane, 4,4xe2x80x2-bicyclohexyldiol;
triols such as: glycerol, 1,3,5-cyclohexantriol;
sugars such as: furanoside and pyranoside sugars such as glucose, fructose;
polymers such as: hydroxyethylcellulose, hydroxypropylcellulose.
Compounds of formula I upon cleavage may also generate antimicrobial compounds. Examples of these compounds are e.g. presented by J. J. Kabara, Cosmet. Sci. Technol. Ser. (16) 1997, p 181-208, especially in Table 8.6.
Of course, the afore mentioned alcohols, phenols and antimicrobial compounds can serve mutually as fragrances and antimicrobial compounds, respectively. A person of skill in the art is well aware of these interrelationships and can make use thereof to solve a specific problem by using the precursors of the present invention.
The compounds of formula Ia are virtually odourless under room temperature and atmospheric conditions, i.e. about 10 to about 40 degrees Celsius and about 20 to 100% relative humidity. However, when applied to the body or when used in an application in the presence of enzymes such as lipases and proteases, or when heated they undergo a transformation in which the alcohol or phenol and lactone are released.
The compounds of formula Ia, upon cleavage, provide alcohols or phenols and lactones having organoleptic properties and therefore permit the development of methods useful in enhancing the odour of consumer products.
Suitable examples of such lactones are listed in Table 2.
6-methyl-pyran-2-one
5-heptyldihydro-2(3H)-furanone*
5-pentyldihydro-2(3H)-furanone*
5-(3-hexenyl)dihydro-5-methyl-(Z)-2(3H)-furanone
5-hexyldihydro-5-methyl-2(3H)-furanone
5-hexyldihydro-2(3H)-furanone*
5-octyldihydro-2(3H)-furanone
8-(1-methylethyl)-1-oxaspiro[4.5]-decan-2-one*
8-methyl-1-oxaspiro[4.5]-decan-2-one
8-ethyl-1-oxaspiro[4.5]-decan-2-one
5-(1,5-dimethyl-4-hexenyl)dihydro-2(3H)-furanone
2-oxo-5-butyl-tetrahydrofuran*
4-methyl-5-pentyl-dihydro-2(3H)-furan-2-one
5-hexyldihydro-5-methyl-2(3H)-furanone
dihydro-5-methyl-5-vinyl-2(3H)-furanone
octahydro-2H-1-benzopyran-2-one
tetrahydro-6-pentyl-2H-pyran-2-one
tetrahydro-6-hexyl-2H-pyran-2-one
tetrahydro-6-heptyl-2H-pyran-2-one
tetrahydro-6-(3-pentenyl)-(E)-2H-pyran-2-one
tetrahydro-6-(2-pentenyl)-(Z)-2H-pyran-2-one
whereby the asterisks indicate the preferred lactones. Table 2 is not complete but shows only representative lactones with positive effect in connection with the present invention. A person skilled in the art is, however, quite aware to further lactones which provide a positive contribution to the enhancement of the odour of consumer products.
The compounds of formula Ia can be prepared by using standard methods known to a person skilled in the art. For example, they can be prepared in two steps from keto acids. Esters of the keto acids may be prepared by standard methods known to those skilled in the art, see Comprehensive Organic Chemistry, Derek Barton and W. David Ollis, eds., Vol. 2, 1979, pp.871-907. For example, esters are formed by the acid catalyzed reaction between a carboxylic acid and an alcohol. During the condensation water is usually removed.
Either protic or Lewis acids may be used. Some acids which may be used are p-toluenesulfonic acid, sulfuric acid, and pyridinium p-toluenesulfonate. A variety of inert solvents may be used such as toluene, xylene, cyclohexane, and hexane.
In another method which may be used for the preparation of the compounds of formula Ia, an appropriate carboxylic acid and an appropriate alcohol react to form an ester when treated with N,Nxe2x80x2-dicyclohexylcarbodiimide and 4-pyrrolidinopyridine, see e.g. the procedure of Hassner and Alexanian, Tetrahedron Letters 4475, (1978).
These esters can then be reduced to the compounds of formula I by using standard methods known to a person skilled in the art. Reagents for the transformation include sodium borohydride and lithium aluminum hydride.
Compounds of formula Ia can also be prepared directly from the corresponding alcohol and lactone, see e.g. J. Org. Chem. (1966), 485.
The most preferred precursor compounds according to the invention are esters of one alcohol out of the group citronellol, phenylethyl alcohol, geraniol and cis-3-hexanol, specifically compounds selected from the group consisting of 4-hydroxy-decanoic acid 2-phenethyl ester, 4-hydroxy-decanoic acid 3,7-dimethyl-oct-6-enyl ester, 4-hydroxy-decanoic acid hex-3-enyl ester, 4-hydroxy-decanoic acid 3,7-dimethyl-oct-2,6-dienyl ester, 5-hydroxy-dodecanoic acid 3,7-dimethyl-oct-6-enyl ester, 5-hydroxy-dodecanoic acid 3,7-dimethyl-oct-2,6-dienyl ester, 4-hydroxy-undecanoic acid 3,7-dimethyl-oct-6-enyl ester, 4-hydroxy undecanoic acid 3,7-dimethyl-oct-2,6 dienyl ester, 4-hydroxy-decanoic acid 1,5-dimethyl-1-vinyl-hex-4-enyl ester, 4-hydroxy-decanoic acid 1,1,5-trimethyl-hept-6-enyl ester, 4-hydroxy-decanoic acid 1,1,5-trimethyl-hexyl ester, 4-hydroxy-undecanoic acid 3,7-dimethyl-oct-6-enyl ester, 4-hydroxy-undecanoic acid phenethyl ester, 4-hydroxy-undecanoic acid hex-3-enyl ester, 4-hydroxy-nonanoic acid 3,7-dimethyl-octa-2,6-dienyl ester, 4-hydroxy-nonanoic acid 3,7-dimethyl-oct-6-enyl ester, 4-hydroxy-nonanoic acid hex-3-enyl ester, 4-hydroxy-nonanoic acid phenethyl ester, 3-(1-hydroxy-4-isopropyl-cyclohexyl)-propionic acid 3,7-dimethyl-octa-2,6-dienyl ester and 4-hydroxy-undecanoic acid 2-(4-hydroxy-undecanoyloxy)-ethyl ester.
Concerning the second group of the precursor compounds according to the invention under activating conditions, the hydroxy amide will cleave to release a lactone and an amine. The lactone may have organoleptic properties.
There are basically three classes of amine products to build the amides according to the invention:
non-odoriferous amines which can be primary or secondary amines and have more than nine carbon atoms. Preferable amines are those with an affinity to fiber and those used in cosmetic and laundry formulations,
odoriferous amines,
non-odoriferous amines substituted with an odoriferous group. For example, the amine may be substituted by a group such as xe2x80x94CO2R, xe2x80x94OCO2R wherein R represents a radical of a fragrant alcohol or the enol form of a fragrant aldehyde or ketone, or any radical that can form another lactone.
Preferred examples of odoriferous amines are:
1-methyl-1-(4-methyl-3-cyclohexen-1-yl)ethyl anthranilic acid; benzopyrrole; 8,8-di(1H-indol-3-yl)-2,6-dimethyl-octane-2-ol; anthranilic acid allyl ester; anthranilic acid 1,5-dimethyl-1-vinyl-4-hexenyl ester; 2-amino-benzoic acid methyl ester*; methyl anthranilic acid N-(2-methylpent-1-en-1-yl) ester; anthranilic acid phenylethyl ester*; 2-methylamino-benzoic acid methyl ester*; 6-methyltetrahydroquinoline; isobutyl N-methyl anthranilate; (Z)-3-hexenyl 2-aminobenzoate*, whereby the asterisks indicate the more preferred odoriferous amides.
A wide variety of non-odoriferous amines can also be used for the preparation of the amides according to the invention. For example, a list of suitable primary and secondary cosmetic amines can be found in the xe2x80x98Cosmetic Ingredient Handbookxe2x80x99 edited by Joanne M. Nikitakis. Suitable surfactant amines can be found, for example, in xe2x80x98Surfactants Europaxe2x80x99 edited by Gordon L. Hollis. Amino acids such as glycine, leucine, tyrosine, serine, glutamic acid, aspartic acid, phenylalanine, alanine, lysine, arginine, histidine, cysteine, valine, proline, tryptophan, isoleucine, methionine, asparagine, glutamine and threonine may also be used.